A simple and efficient synthesis of substituted 2,2′-bithiophene and 2,2′:5′,2″-terthiophene

Article abstract of DOI:10.1021/ol500356w

A simple and efficient approach is developed for the synthesis of substituted 2,2′-bithiophene- and 2,2′:5′,2″- terthiophene-5-carboxylic acids and esters which is based on thiophene ring closure in the Fiesselmann reaction. Using this method, derivatives containing a long alkyl chain with or without an end functional group or an aryl substituent can be conveniently prepared.

Full text of DOI:10.1021/ol500356w

Letter
pubs.acs.org/OrgLett
A Simple and Efficient Synthesis of Substituted 2,2′-Bithiophene and
2,2′:5′,2″-Terthiophene
Anastasia S. Kostyuchenko,†,‡ Alexey M. Averkov,† and Alexander S. Fisyuk†,*,‡
†Department of Organic Chemistry, Omsk F. M. Dostoevsky State University, Mira Ave., 55a, 644077 Omsk, Russia
‡Laboratory of New Organic Materials, Omsk State Technical University, Mira Ave., 11, 644050 Omsk, Russia
S
* Supporting Information
ABSTRACT: A simple and efficient approach is developed for the
synthesis of substituted 2,2′-bithiophene- and 2,2′:5′,2″-terthiophene-5-
carboxylic acids and esters which is based on thiophene ring closure in
the Fiesselmann reaction. Using this method, derivatives containing a
long alkyl chain with or without an end functional group or an aryl
substituent can be conveniently prepared.
Scheme 1. Synthesis of 3-Alkyl(aryl)-2,2′-bithiophene-5-
carboxylate Starting from Thiophene by the “Building
Blocks” Approach
unctionalized bi- and terthiophenes are important building
Fblocks for the synthesis of fluorescent markers for
biological applications1 and π-conjugated oligomers and
polymers which are used in organic electronics as active layers
in various devices such as organic light-emitting diodes, optical
switches, solar cells, field effect transistors, etc.2 They are also
precursors to biologically active compounds.3
There are two general strategies for the synthesis of bi- and
terthiophenes and similar conjugated compounds: the “building
blocks” approach and the “ring closure” approach. In the first
one, oxidative coupling or transition metal catalyzed cross-
coupling reactions,4 such as Stille,4b,c Suzuki,4b,d−f etc., are used
for the thiophene−thiophene bond formation. Despite the fact
that the “building blocks” approach is more popular, it is
limited by the number of commercially available building
blocks. Their low diversity and limited availability lead to
decreasing efficiency of this approach. For example, a
palladium-catalyzed Stille reaction was employed for the
cross-coupling of 5-bromo-4-alkylthiophene-2-carboxylate
ester with an appropriate thiophene organostannane to
generate 3-alkyl-2,2′-bithiophene-5-carboxylate ester.5 In this
case, methyl 5-bromo-4-alkylthiophene-2-carboxylates are used
as building blocks.
The known method for the preparation of these compounds
starting from thiophene includes the synthesis of 3-bromothio-
phene6a (two steps), 3-alkylthiophene, and 2-bromo-3-alkyl-
thiophem5a,6b and then carboxylation and etherification5a
(Scheme 1). The last steps of this synthesis require the use
of toxic reagents (organostannans, palladium catalysts) at low
temperatures.
closure reaction using reagents, which contain additional
conjugated aromatic rings as substituents.4a,7
In this paper we present this approach in which the
Fiesselmann8 reaction of ring closure is exploited in the
synthesis of 3,5-substituted 2,2′-bithiophene- and 3-substituted
2,2′:5′,2″-terthiophene-5-carboxylic acids and esters.
Ketones 2a−e were obtained by the reaction of thiophene
and the corresponding carboxylic acids 1a−e in the presence of
trifluoroacetic anhydride.9
An alternative strategy for the synthesis of bi- and
terthiophenes, proposed here, is based on the thiophene ring
Received: February 3, 2014
Published: March 13, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
2-Hexylthiophene, bithiophene, and lauric acid chloro-
anhydride in the presence of SnCl4 were used for the synthesis
of (5-hexyl-2-thienyl)dodecan-1-one 2f and 1-(2,2′-bithien-5-
yl)dodecan-1-one 2g (Scheme 2). The yields of 2a−g were in
the range of 67−88%.
mercaptoacetate in the presence of sodium ethoxide in ethanol
under reflux with yields of 55−93%. Hydrolysis of 7a−f in
ethanol containing sodium hydroxide led to the formation of
carboxylic acids 8a−f with yields of 70−93% (Scheme 4).
Scheme 4. Synthesis of Substituted 2,2′-Bithiophene- and
2,2′:5′,2″-Terthiophene-5-carboxylic Acids and Esters
Scheme 2. Synthesis of Thienyl Ketones 2a−f
Compounds 2f, 6a−c,f, and 7a,b,f,g were obtained in the
form of an oil and purified by column chromatography on silica
gel. The solid products 2e,g, 6d,e,g, 7c,d,e, and 8a−g were
recrystallized from suitable solvents. All intermediate and final
products were identified by elemental analysis, NMR, and IR.
To conclude, we have elaborated a simple and efficient
method for the synthesis of substituted 2,2′-bithiophene- and
2,2′:5′,2″-terthiophene-5-carboxylic acids and esters containing
an alkyl chain with or without an end functional group or an
additional aryl substituent.
This method, being more versatile than those previously
reported, is based on the thiophene ring closure using the
Fiesselmann reaction. In particular, compounds 7 and 8 can be
obtained in good yields from commercial reagents in only three
and four steps, respectively.
Thienyl ketones 2a−g were converted to acrylaldehydes 6a−
g via the Vilsmeier−Haack−Arnold reaction with phosphorus
oxychloride in dimethylformamide. Products were purified by
column chromatography and identified by elemental analysis
and spectroscopic means (NMR and FTIR). Compounds 6a−g
were obtained as mixtures of Z- and E-isomers with the total
yields ranging from 67% to 87% (see Scheme 3 and Table 1).
Scheme 3. Chloroformylation of Thienyl Ketones 2a−g
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and full spectroscopic data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: fisyuk@chemomsu.ru.
Notes
Table 1. Yields of Products 2, 6−8
entry product
R
R1
2
Z,E-6
7
8
The authors declare no competing financial interest.
1
2
3
4
5
6
7
a
b
c
d
e
f
Me
H
H
H
H
H
84
87
88
45
69
67
75
87
78
70
71
67
84
80
83
76
55
82
93
80
93
79
78
70
88
83
ACKNOWLEDGMENTS
n-C6H13
Ph
■
This work was supported by the Russian Foundation for Basic
Research (12-03-98013-p_sibiria_a). The authors would like to
thank Prof. Adam Pron (Warsaw University of Technology) for
constructive discussions.
C6H3(OMe)2
(CH2)4NHCOPh
n-C10H21
n-C6H13 67
thienyl 71
g
n-C10H21
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